Suppression of human epidermal growth factor receptor 2 via interference increases the chemosensitivity of ovarian carcinoma

通过干扰抑制人类表皮生长因子受体 2 可增加卵巢癌的化学敏感性

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作者:Xiaoping Song, Kailv Sun, Jianming Hu, Jianghu Zhou

Abstract

The function of human epidermal growth factor receptor 2 (HER2) in the chemosensitivity of ovarian carcinoma has not been fully investigated, therefore, the present study aimed to analyze the potential role of HER2 in ovarian carcinoma chemosensitivity in further detail. SKOV3 cells were transfected with lentiviral-mediated HER2-small hairpin RNA (shRNA) molecules to establish the stable expression of HER2-shRNA in the SKOV3 cell line (knockdown cells; KD) and negative control cell line (NC). The untransfected SKOV3 cell line served as the blank control (CON) group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression of HER2 in the three different cell types, which were subsequently examined for growth inhibition using a cell counting kit-8 assay. The CON and KD cell strains were utilized to establish xenograft models in nude mice, primarily to detect the expression of the HER2 protein, and additionally to observe tumor size changes under the treatment of cisplatin (DDP) chemotherapy. RT-qPCR and western blot analysis demonstrated a significant decrease in the levels of HER2 mRNA and protein in the KD cells. The suppression of HER2 expression resulted in an increase of chemotherapy sensitivity in the SKOV3 cells. HER2 protein expression decreased significantly following transduction with specific HER2-shRNA. Additionally, growth slowed significantly under treatment with DDP in ovarian cancer transplantation tumors. In conclusion, lentivirus-mediated HER2-shRNA effectively inhibits the expression of the HER2 gene, and increases the chemosensitivity to DDP in ovarian carcinoma.

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